Pregabalin, a new type antagonist of γ-aminobutyric acid (GABA) receptor, is developed by Pfizer. It was approved by European Union for the first time in July 2004 for treating partial seizure in adult patients, and the trade name thereof is Lyrica. In June 2005, it was approved for sale in the US by US Food and Drug Administration (FDA). Indications thereof were added in March 2006 for treating generalized anxiety disorder and social anxiety disorder. In 2009, it was approved additionally for treating spinal cord injury, trauma, multiple sclerosis, diabetic neuropathic pain and shingles neuropathic pain, which further extends its clinical application. Since Pregabalin has good effects on anti-epilepsy, anti-anxiety and treating neuropathic pain and the like, it has been widely used in clinical treatment currently, and the market demand further increased. According to a survey, Pregabalin on the market is mostly synthesized by using the method of chemical synthesis currently.
The 3-carbamoylmethyl-5-methylhexanoic acid is a key intermediate for preparing Pregabalin, and the structure formula thereof is shown as follow.

In the process of preparing Pregabalin, the (S) type isomer of 3-carbamoylmethyl-5-methylhexanoic acid is used. Currently, most of the literatures have reported this levoisomer is obtained by using a resolution method with a resolving agent. However, the yield of resolving 3-carbamoylmethyl-5-methylhexanoic acid to (S)-3-carbamoylmethyl-5-methylhexanoic acid is only about 35%, and a great quantity of raw materials remain in the resolving mother liquor (i.e., the utilization rate of 3-carbamoylmethyl-5-methylhexanoic acid is about 35%). When Pregabalin is produced commercially on large scale, about 65% of the intermediate will remain in the mother liquor if not considering the recycle of mother liquor, which results in waste, and thereby enormously increases the cost for producing Pregabalin. In India Anil B. Chavan et al. mentioned reusing 3-carbamoylmethyl-5-methylhexanoic acid in the mother liquor by using a racemization recycle method in the article “An Efficient Process of Racemization of 3-(Carbamoylmethyl)-5-methylhexanoic acid: A Pregabalin Intermediate” (see Organic process research and Development, Vol 13, No. 4, Page 812-814, May 18, 2009). In such methods, alkali liquor is usually added into mother liquor at first, layered, and then pH is adjusted. The wet product is filtered, then toluene is added, and then diisopropylamine, 1,8-diazabicyclo-undec-7-ene (DBU), diisopropylethylamine and the like are added to reflux and react for racemization. Then alkali is used for the ring-opening reaction, pH is adjusted, and the reactant is filter, refine by ethyl acetate, and dry (total yield: about 50% by the amount of 3-carbamoylmethyl-5-methylhexanoic acid added in the resolution). This method is cumbersome and lengthy, and the operation is complicated, requiring twice pH adjustment, which introduces large quantity of inorganic salts, and produces waste water.